D-D4FC（β-D-2′，3′-双脱氢双脱氧-5-氟胞嘧啶核苷）是一种新型抗 HIV 病毒的核苷类药物，目前正在美国、法国和德国进行 Ⅱ 期临床。利用乳酸杆菌提取的粗制 N-脱氧核糖转移酶实现了由 D4T（β-D-2′，3′-双脱氢双脱氧-胸苷，司他夫定）和 5-FC（5-氟胞嘧啶）合成 D-D4FC，转化率达到 25%。现在，发现利用乳酸杆菌整细胞也可实现此反应，其转化率经过 12.5 h 可达到 50%，更有利于可能的工业化连续生产。研究了整细胞催化合成 D-D4FC 反应中，pH 值、缓冲液类型、底物浓度、加菌量、反应时间等条件的影响并进行了优化，探讨了反应中乳酸杆菌整细胞催化的可能机理。
Abstract:
D-D4FC (β-D-2′，3′-didehydro-2′，3′-dideoxy-5-fluorocytidine)，a new anti-HIV drug，is on its PhaseⅡ clinical trials in America，France and Germany. Our lab has synthesized D-D4FC successfully using N-deoxyribosyltransferase from Lactobacillus helveticto catalyzing the ribose transfer from D4T (β-D-2′，3′-unsaturated thymidine) to 5-FC (5-fluorocytidine).The yield of D-D4FC reached 25%.We discovered the reaction could also be done by using intact cells.The yield could increase to 50% in 12.5 hours and more convenient to industrial continuous process.In this paper，the conditions including pH，buffer，substrates concentration，cells amount，reaction time and a possible catalytic mechanism were studied and discussed.
